Liver Transplant and Combined Liver-Kidney Transplant

POLICY NUMBER

A.7.03.06

DESCRIPTION

Liver transplantation is currently the treatment of last resort for patients with end-stage liver disease. Liver transplantation may be performed with a liver donation after a brain or cardiac death or with a liver segment donation from a living donor. Individuals are prioritized for transplant by mortality risk and severity of illness criteria developed by the Organ Procurement and Transplantation Network and the United Network of Organ Sharing. The severity of illness is determined by the Model for End-stage Liver Disease and Pediatric End-stage Liver Disease scores.

Solid organ transplantation offers a treatment option for patients with different types of end stage organ failure that can be lifesaving or provide significant improvements to a patient’s quality of life. Many advances have been made in the last several decades to reduce perioperative complications. Available data supports improvement in long-term survival as well as improved quality of life particularly for liver, kidney, pancreas, heart, and lung transplants. Allograft rejection remains a key early and late complication risk for any organ transplantation. Transplant recipients require life-long immunosuppression to prevent rejection. Patients are prioritized for transplant by mortality risk and severity of illness criteria developed by Organ Procurement and Transplantation Network and United Network of Organ Sharing.

Liver Transplantation

Liver transplantation is routinely performed as a treatment of last resort for patients with end-stage liver disease. Liver transplantation may be performed with liver donation after a brain or cardiac death or with a liver segment donation from a living donor. Certain populations are prioritized as Status 1A (eg, acute liver failure with a life expectancy of fewer than 7 days without a liver transplant) or Status 1B (pediatric patients with chronic liver disease). Following Status 1, donor livers are prioritized to those with the highest scores on the Model for End-stage Liver Disease (MELD) and Pediatric End-stage Liver Disease (PELD) scales. Due to the scarcity of donor livers, a variety of strategies have been developed to expand the donor pool. For example, a split graft refers to dividing a donor liver into 2 segments that can be used for 2 recipients. Living donor (LD) liver transplantation (LT) is now commonly performed for adults and children from a related or unrelated donor. Depending on the graft size needed for the recipient, either the right lobe, left lobe, or the left lateral segment can be used for LD LT. In addition to addressing the problem of donor organ scarcity, LD LT allows the procedure to be scheduled electively before the recipient's condition deteriorates or serious complications develop. Living donor LT also shortens the preservation time for the donor liver and decreases disease transmission from donor to recipient.

Solid organ transplants are a surgical procedure and, as such, are not subject to regulation by the U.S. Food and Drug Administration (FDA).

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation Title 21, parts 1270 and 1271. Solid organs used for transplantation are subject to these regulations.

POLICY

No benefits will be provided for a covered transplant procedure unless the Member receives prior authorization through case management from Blue Cross & Blue Shield ofMississippi.

A liver transplant, using a cadaver or living donor, may be considered medically necessary for carefully selected individuals with end-stage liver failure due to irreversibly damaged livers.

Etiologies of end-stage liver disease include, but are not limited to, the following:

1.  Hepatocellular diseases

• Alcoholic liver cirrhosis

• Viral hepatitis (either A, B, C, or non-A, non-B)

• Autoimmune hepatitis

• Alpha-1 antitrypsin deficiency

• Hemochromatosis

• Non-alcoholic steatohepatitis

• Protoporphyria

• Wilson's disease 

2.  Cholestatic liver diseases

• Primary biliary cirrhosis

• Primary sclerosing cholangitis with development of secondary biliary cirrhosis

• Biliary atresia 

3.  Vascular disease

• Budd-Chiari syndrome

4.  Primary hepatocellular carcinoma (see Policy Guidelines section for individuals selection criteria)

5.  Inborn errors of metabolism

6.  Trauma and toxic reactions

7.  Miscellaneous

• Familial amyloid polyneuropathy.

Liver transplantation may be considered medically necessary in individuals with polycystic disease of the liver who have massive hepatomegaly causing obstruction or functional impairment.

Liver transplantation may be considered medically necessary in individuals with unresectable hilar cholangiocarcinoma (see Policy Guidelines for individual selection criteria).

Liver transplantation may be considered medically necessary in pediatric individuals with nonmetastatic hepatoblastoma.

Liver retransplantation may be considered medically necessary in individuals with:

• primary graft non-function

• hepatic artery thrombosis

• chronic rejection

• ischemic type biliary lesions after donation after cardiac death

• recurrent non-neoplastic disease causing late graft failure.

Combined liver-kidney transplantation may be considered medically necessary in individuals who qualify for liver transplantation and have advanced irreversible kidney disease.

Liver transplantation is considered investigational in the following situations:

• Individuals with intrahepatic cholangiocarcinoma

• Individuals with neuroendocrine tumors metastatic to the liver.

Liver transplantation is considered investigational in the following individuals:

• Individuals with hepatocellular carcinoma that has extended beyond the liver (see Policy Guidelines section for individual selection criteria)

• Individuals with ongoing alcohol and/or drug abuse. (Evidence for abstinence may vary among liver transplant programs, but generally a minimum of 3 months is required.)

Liver transplantation is considered investigational in all other situations not described above.

HIV positivity is not an absolute contraindication to transplant. Each individual transplant center will determine patient selection criteria for HIV positive patients.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Contraindications

Potential contraindications for solid organ transplant are subject to the judgment of the transplant center and include the following:

1. Known current malignancy, including metastatic cancer

2. Recent malignancy with high risk of recurrence

3. Untreated systemic infection making immunosuppression unsafe, including chronic infection

4. Other irreversible end-stage diseases not attributed to liver disease

5. History of cancer with a moderate risk of recurrence

6. Systemic disease that could be exacerbated by immunosuppression

7. Psychosocial conditions or chemical dependency affecting ability to adhere to therapy.

Liver-Specific Criteria

The Model for End-stage Liver Disease (MELD) and Pediatric End-stage Liver Disease (PELD) scores range from 6 (less ill) to 40 (gravely ill). The MELD and PELD scores will change during an individual's tenure on the waiting list.

Individuals with liver disease related to alcohol or drug abuse must be actively involved in a substance abuse treatment program.

Tobacco consumption is a contraindication.

Individuals with polycystic disease of the liver do not develop liver failure but may require transplantation due to the anatomic complications of a hugely enlarged liver. The MELD and PELD score may not apply to these cases. One of the following complications should be present:

• Enlargement of liver impinging on respiratory function

• Extremely painful enlargement of liver

• Enlargement of liver significantly compressing and interfering with function of other abdominal organs.

Individuals with familial amyloid polyneuropathy do not experience liver disease per se, but develop polyneuropathy and cardiac amyloidosis due to the production of a variant transthyretin molecule by the liver. MELD and PELD exception criteria and scores may apply to these cases. Candidacy for liver transplant is an individual consideration based on the morbidity of the polyneuropathy. Many individuals may not be candidates for liver transplant alone due to coexisting cardiac disease.

Hepatocellular Carcinoma

Criteria used for selection of hepatocellular carcinoma individuals eligible for liver transplant include the Milan criteria, which is considered the criterion standard, the University of California, San Francisco expanded criteria, and United Network of Organ Sharing (UNOS) criteria.

Milan Criteria

A single tumor 5 cm or less or 2 to 3 tumors 3 cm or less.

University of California, San Francisco Expanded Criteria

A single tumor 6.5 cm or less or up to 3 tumors 4.5 cm or less, and a total tumor size of 8 cm or less.

United Network for Organ Sharing Stage T2 Criteria

A single tumor 2 cm or greater and up to 5 cm or less or 2 to 3 tumors 1 cm or greater and up to 3 cm or less and without extrahepatic spread or macrovascular invasion. United Network for Organ Sharing (UNOS) criteria were updated in 2022.

Individuals with hepatocellular carcinoma are appropriate candidates for liver transplant only if the disease remains confined to the liver. Therefore, the individual should be periodically monitored while on the waiting list, and if metastatic disease develops, the individual should be removed from the transplant waiting list. Also, at the time of transplant, a backup candidate should be scheduled. If locally extensive or metastatic cancer is discovered at the time of exploration prior to hepatectomy, the transplant should be aborted, and the backup candidate scheduled for transplant.

Note that liver transplantation for those with T3 HCC is not prohibited by UNOS guidelines, but such individuals do not receive any priority on the waiting list. All individuals with HCC awaiting transplantation are reassessed at 3-month intervals. Those whose tumors have progressed and are no longer stage T2 will lose the additional allocation points.

Additionally, nodules identified through imaging of cirrhotic livers are given a class 5 designation. Class 5B and 5T nodules are eligible for automatic priority. Class 5B criteria consists of a single nodule 2 cm or larger and up to 5 cm (T2 stage) that meets specified imaging criteria. Class 5T nodules have undergone subsequent locoregional treatment after being automatically approved on initial application or extension. A single class 5A nodule (>1 cm and <2 cm) corresponds to T1 HCC and does not qualify for automatic priority. However, combinations of class 5A nodules are eligible for automatic priority if they meet stage T2 criteria. Class 5X lesions are outside of stage T2 and ineligible for automatic exception points. Nodules less than 1 cm are considered indeterminate and are not considered for additional priority. Therefore, the UNOS allocation system provides strong incentives to use locoregional therapies to downsize tumors to T2 status and to prevent progression while on the waiting list.

Human Immunodeficiency Virus-Positive Patients

The American Society of Transplantation (2019) published a guideline on solid organ transplantation in HIV-infected patients. For liver transplants, the following criteria for transplantation are suggested:

• Cluster of differentiation 4 (CD4) count >100 cells/mL with no history of acquired immunodeficiency syndrome (AIDS)-defining illnesses such as opportunistic infection or malignancy or CD4 count >200 cells/mL for at least 3 months

• Undetectable HIV viral load while receiving antiretroviral therapy or a detectable HIV viral load in patients with intolerance to antiretroviral therapy that can be suppressed post-transplant

• Documented compliance with a stable antiretroviral therapy regimen

• Absence of active opportunistic infection and malignancy

• Absence of chronic wasting or severe malnutrition

• Appropriate follow-up with providers experienced in HIV management and ready access to immunosuppressive medication therapeutic drug monitoring.

Cholangiocarcinoma

According to the Organ Procurement and Transplantation Network (OPTN) policy on liver allocation, candidates with cholangiocarcinoma meeting the following criteria will be eligible for a MELD or PELD exception with a 10% mortality equivalent increase every 3 months:

• Centers must submit a written protocol for patient care to the OPTN and UNOS Liver and Intestinal Organ Transplantation Committee before requesting a MELD score exception for a candidate with cholangiocarcinoma. This protocol should include selection criteria, administration of neoadjuvant therapy before transplantation, and operative staging to exclude individuals with regional hepatic lymph node metastases, intrahepatic metastases, and/or extrahepatic disease. The protocol should include data collection as deemed necessary by the OPTN and UNOS Liver and Intestinal Organ Transplantation Committee.

• Candidates must satisfy diagnostic criteria for hilar cholangiocarcinoma: malignant-appearing stricture on cholangiography and one of the following: carbohydrate antigen 19-9 100 U/mL, or biopsy or cytology results demonstrating malignancy, or aneuploidy. The tumor should be considered unresectable on the basis of technical considerations or underlying liver disease (e.g., primary sclerosing cholangitis).

• If cross-sectional imaging studies (computed tomography scan, ultrasound, magnetic resonance imaging) demonstrate a mass, the mass should be less than 3 cm.

• Intra- and extrahepatic metastases should be excluded by cross-sectional imaging studies of the chest and abdomen at the time of initial exception and every 3 months before score increases.

• Regional hepatic lymph node involvement and peritoneal metastases should be assessed by operative staging after completion of neoadjuvant therapy and before liver transplantation. Endoscopic ultrasound-guided aspiration of regional hepatic lymph nodes may be advisable to exclude individuals with obvious metastases before neoadjuvant therapy is initiated.

• Transperitoneal aspiration or biopsy of the primary tumor (either by endoscopic ultrasound, operative, or percutaneous approaches) should be avoided because of the high risk of tumor seeding associated with these procedures.

Living Donor Criteria

Donor morbidity and mortality are prime concerns in donors undergoing right lobe, left lobe, or left lateral segment donor partial hepatectomy as part of living donor liver transplantation. Partial hepatectomy is a technically demanding surgery, the success of which may be related to the availability of an experienced surgical team. The American Society of Transplant Surgeons proposed the following guidelines for living donors:

• They should be healthy individuals who are carefully evaluated and approved by a multidisciplinary team including hepatologists and surgeons to assure that they can tolerate the procedure.

• They should undergo evaluation to ensure that they fully understand the procedure and associated risks.

• They should be of legal age and have sufficient intellectual ability to understand the procedures and give informed consent.

• They should be emotionally related to the recipients.

• They must be excluded if the donor is felt or known to be coerced.

• They need to have the ability and willingness to comply with long-term follow-up.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

8/1998: Approved by Medical Policy Advisory Committee (MPAC).

2/2001: Reviewed by MPAC; The evidence of abstinence for a minimum of 6 months will no longer be required.

7/9/2001: Code Reference section updated; 356.0, 459.9, 576.2 and 576.8 ICD-9 diagnosis codes deleted.

2/14/2002: Investigational definition added.

5/1/2002: Type of Service and Place of Service deleted.

5/14/2002: Description and Policy Guidelines sections revised; UNOS status categories deleted.

7/21/2005: Reviewed by MPAC; "HIV positivity is not an absolute contraindication to transplant. Each individual transplant center will determine patient selection criteria for HIV positive patients."

10/17/2005: Code Reference table updated; codes S2152, 47140, 47141, 47142, 47143, 47144, 47145, 47146, 47147 added. V59.6, 285.0, 751.62 deleted; ICD-9 procedure codes 00.91, 00.92, 00.93 added; diagnosis codes 070.70, 070.71, 273.4, 279.4 added. Deleted Non-Covered Codes table.

10/25/2005: Description revised for CPT-4 codes: 47133, 47135, 47136. Description revised for ICD-9 diagnosis codes: 070.0, 070.1, 070.20-070.23, 070.30-070.33, 070.51- 070.54, 070.59, 121.1, 121.3, 155.0, 270.0-270.9, 271.0-271.4, 271.8, 271.9, 272.0-272.9, 275.0, 275.1, 277.1, 277.3, 357.4, 571.6, 573.1, 573.2, 573.3. ICD-9 Diagnosis codes range detailed: 864.00-864.05, 864.09-864.15, 864.19. 

03/14/2006: Coding updated. CPT4 2006 revisions added to policy.

9/13/2006: Coding updated. ICD9 2006 revisions added to policy.

12/19/2008: Policy reviewed, no changes.

9/28/2009: Code reference section updated. New ICD-9 diagnosis codes 279.41 and 279.49 added to covered table. Deleted statement added to ICD-9 diagnosis code 279.4 deleted as of 10-1-2009.

10/14/2010: Annual ICD-9 code update: 275.0 deleted/expanded to the fifth digit. Added 275.01 - 275.09 to the Covered Codes table.

12/13/2011: Policy description updated. Added Biliary atresia to the medically necessary policy statement. Added neuroendocrine tumor metastases to investigational statement. Policy statement regarding hepatocellular carcinoma that has extended beyond the liver, active infection, and ongoing alcohol and/or drug abuse was changed from investigational to not medically necessary. Deleted outdated references from the Sources section.

04/18/2013: Policy statement revised to add alcoholic steatohepatitis cirrhosis as medically necessary, to add medically necessary indications for retransplantation, and to indicate that extrahepatic peri-hilar or hilar cholangiocarcinoma may be considered medically necessary. Other intrahepatic or extrahepatic malignancies including non-peri-hilar or non-hilar cholangiocarcinoma and recurrent hepatocellular carcinoma salvage treatment added to the investigational policy statement. Added potential contraindications to transplant and cholangiocarcinoma selection criteria to the policy guidelines.

05/22/2014: Policy reviewed; description updated. Policy statement regarding a liver transplant using a cadaver or living donor changed from "is" medically necessary to "may be considered" medically necessary. Policy statement revised to move polycystic disease of the liver to a separate policy statement: "Liver transplantation may be considered medically necessary in patients with polycystic disease of the liver who have massive hepatomegaly causing obstruction or functional impairment." Added policy statement that liver transplantation may be considered medically necessary in pediatric patients with nonmetastatic hepatoblastoma. Added investigational statement that liver transplantation is considered investigational in all other situations not described. Policy statement revised to remove "patients with an active infection" from the list of indications when liver transplantation is considered not medically necessary. Policy guidelines updated to add the MELD and PELD score range and to note that these scores may or may not apply to certain cases. Removed deleted ICD-9 codes 275.0, 277.3, and 279.4 from the Code Reference section.

02/16/2015: Policy reviewed; description updated regarding pediatric patients. Added the following statement to the policy statement section: *See Policy Guidelines section for patient selection criteria. Policy guidelines updated regarding selection criteria for hepatocellular carcinoma patients and donor criteria for living donor liver transplant.

08/27/2015: Code Reference section updated for ICD-10.

12/31/2015: Code Reference section updated to add CPT code 47399.

06/01/2016: Policy number A.7.03.06 added. Policy Guidelines updated to add medically necessary and investigative definitions.

09/30/2016: Code Reference section updated to add new ICD-10 diagnosis codes E78.00 and E78.01.

09/29/2017: Code Reference section updated to add new ICD-10 diagnosis codes E85.81, E85.82, and E85.89, effective 10/01/2017. Removed deleted CPT code 47136 and ICD-10 diagnosis code E78.0.

02/26/2018: Policy title changed from "Liver Transplant" to "Liver Transplant and Combined Liver-Kidney Transplant." Policy description updated regarding FDA regulation. Added statement that combined liver-kidney transplantation may be considered medically necessary in patients who qualify for liver transplantation and have advanced irreversible kidney disease. Policy Guidelines updated to state that patients with liver disease related to alcohol or drug abuse must be actively involved in a substance abuse treatment program. Added contraindication for tobacco and information regarding HIV-positive patients.

10/01/2018: Policy description updated regarding MELD and PELD scales. Policy statements unchanged. Policy Guidelines updated regarding UNOS Stage T2 Criteria. Code Reference section updated to add new ICD-10 diagnosis codes E72.89 and K83.01. Removed deleted ICD-10 diagnosis code E85.8.

09/12/2019: Policy reviewed; no changes.

09/14/2020: Policy description updated regarding solid organ transplantation. Policy statements unchanged. Code Reference section updated to remove deleted ICD-10 diagnosis codes E72.8 and K83.0. Removed deleted ICD-9 code 576.1.

12/20/2021: Policy reviewed. Policy statements unchanged. Policy Guidelines updated with minor changes. Code Reference section updated to remove deleted ICD-10 diagnosis codes E70.8 and E74.8.

11/07/2022: Policy reviewed. Policy statements unchanged. Policy Guidelines updated to change "patients" to "individuals."

10/06/2023: Policy reviewed. Policy statement updated to change "not medically necessary" to "investigational." Policy Guidelines updated to change "patients" to "individuals."

10/21/2024: Policy description updated to change "Patients" to "Individuals." Policy statements unchanged.

10/01/2025: Code Reference section updated to add new ICD-10 diagnosis codes E72.530, E72.538, E72.539, S31.606A, S31.606D, S31.606S, S31.607A, S31.607D, S31.607S, S31.60AA, S31.60AD, and S31.60AS.

SOURCE(S)

Blue Cross Blue Shield Association policy # 7.03.06

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

Appendix

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.